Dimeric 1,4-Dihydropyridines as Calcium Channel Antagonists

Article abstract of DOI:10.1021/jm00403a002

A series of 1,n-alkanediylbis(1,4-dihydropyridines) (n = 2, 4, 6, 8, 10, 12) bridged at C3 of 2,6-dimethyl-3-carboxy-5-carbethoxy-4-(3-nitrophenyl)-1,4-dihydropyridine were synthesized and evaluated in a radioligand binding assay, <3H>nitrendipine in intestinal smooth muscle, as C²⁺ channel ligands.Binding activity was comparable to that of nitrendipine itself but independent of chain length, suggesting the lack of a major binding contribution by the second 1,4-dihydropyridine group.Analogues lacking the second 1,4-dihydropyridine nucleus or possessing an inactive function (4-nitrophenyl) were no less active, confirming that this series of ligands likely does not bridge adjacent 1,4-dihydropyridine receptors of the Ca²⁺ channel.